Ion detection methods, mass spectrometry analysis methods, and mass spectrometry instrument circuitry

ABSTRACT

Ion detection methods are provided that can include applying a first voltage between a power source and a dynode, and contacting the dynode with first ions to create a first charged species. After applying the first voltage, a second voltage can be applied between the power source and the dynode, and the dynode can be contacted with second ions to create a second charged species. Mass spectrometry instrument circuitry is also provided that can include a power source coupled to a dynode via at least one switch with the switch being operatively configured in one position to apply a first voltage between the dynode and the power source, and, in another position, configured to apply a second voltage between the dynode and the power source. Mass spectrometry analysis methods are also provided that can include detecting sorted ions using a dynode configured according to an ion detection parameter with the ion detection parameter including first and second dynode values associated with first and second time values. Methods and circuitry for portable instrumentation are also provided.

CLAIM FOR PRIORITY

This application claims priority to U.S. provisional patent applicationSer. No. 60/500,543 filed Sep. 5, 2003, entitled “Analysis Methods andDevices”, the entirety of which is hereby incorporated by reference.

RELATED PATENT DATA

This application is a 35 U.S.C. §371 of and claims priority to PCTInternational Application Number PCT/US04/129127, which was filed 3 Sep.2004, and was published in English, which claims priority under 35U.S.C. §119 to U.S. Provisional Patent Application No. 60/500,543 whichwas filed 5 Sep. 2003, the entirety of each are incorporated herein byreference.

GOVERNMENT RIGHTS STATEMENT

This invention was made with Government support under SBIR Phase IIContract DABJ19-03-C0001 awarded by the United States Army. TheGovernment has certain rights in the invention.

TECHNICAL FIELD

The present disclosure relates generally to instrumentation, iondetection methods, mass spectrometry analysis methods, and massspectrometry instrument circuitry.

BACKGROUND ART

Mass spectrometry is a valuable analytical technique that may be used todetermine the structures of a wide variety of complex chemical species.In particular aspects, this analytical technique may also be utilized todetermine the quantity of chemical species as well. Mass spectrometrycan also be utilized to provide high-speed analysis of complex mixturesenhancing capacity for structure elucidation. High-capacity andhigh-speed analysis can be two important factors in analyticalinstrumentation.

Mass spectrometers can be configured to ionize a sample and producepositive and/or negative ions which are typically filtered with the aidof a mass analyzer before being detected by a sensor configured todetect ions having specific polarities. Instruments that are capable ofdetecting both positively charged and negatively charged analytes aredesirable. For example, U.S. Pat. No. 4,810,882 to Bateman describesmethods and apparatuses for detecting both positive and negative ionsusing two different electrodes each having their own power supply, andthe teachings of Bateman are hereby incorporated by reference. U.S. Pat.No. 4,966,422 to Mitsui et al. describes the detection of both positiveand negative analytes using two detectors, and the teachings of Mitsuiare hereby incorporated by reference.

Recently, mass spectrometry instruments are being miniaturized for thepurposes of operating the instruments in the field. Miniaturizinginstruments in this fashion allows users to perform analysis actually atthe sample site, which can alleviate difficulties often associated withsample preparation and transport, and thereby reduce errors in analysis.One of the challenges faced when miniaturizing a mass spectrometer ismanufacturing a device that is compact yet versatile.

Aspects of this disclosure provide ion detection methods, massspectrometry analysis methods, and mass spectrometry instrumentcircuitry.

SUMMARY

Ion detection methods are provided that can include providing a detectorbeing operatively aligned to receive charged species from a dynodeoperatively aligned to receive both first and second ions. A firstvoltage can be applied between the dynode's power source and the dynode,in one aspect, and the dynode can be contacted with the first ions tocreate a first charged species. According to one embodiment, afterapplying the first voltage, a second voltage, not equaling the firstvoltage, can be applied between the power source and the dynode, and thedynode can be contacted with the second ions to create a second chargedspecies.

Mass spectrometry instrument circuitry is provided that can include apower source coupled to a dynode via at least one switch operativelyconfigured in one position to apply a first voltage between the dynodeand the power source, and, in another position, to apply a secondvoltage between the dynode and the power source.

Mass spectrometry analysis methods are also provided that can includeionizing a sample to form both first and second ions according to anionization parameter and sorting the ions by mass-to-charge ratioaccording to a mass separation parameter. Methods also provide fordetecting the sorted ions using a dynode configured according to an iondetection parameter including first and second dynode values associatedwith first and second time values. The detecting can also includeacquiring a sample data set comprising a first abundance of ionsacquired during the first time value and a second abundance of ionsacquired during the second time value. Embodiments of the methods andcircuitry described can be utilized in and/or by mass spectrometryinstrumentation and, in particular embodiments, this instrumentation canbe used in the field.

BRIEF DESCRIPTION OF THE DRAWINGS

Aspects of the disclosure are described below with reference to thefollowing accompanying drawings.

FIG. 1 is a block diagram of an instrument according to one embodiment.

FIG. 2 a is a detector diagram according to one embodiment.

FIG. 2 b is a detector diagram according to one embodiment.

FIG. 3 a is a detector diagram according to one embodiment.

FIG. 3 b is a detector diagram according to one embodiment.

FIG. 4 a is a detector diagram according to one embodiment.

FIG. 4 b is a detector diagram according to one embodiment.

FIG. 5 a is data acquired according to one embodiment.

FIG. 5 b is data acquired according to one embodiment.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In one embodiment mass spectrometry analysis methods are provided thatinclude ionizing a sample to form both first and second ions accordingto an ionization parameter, with the first and second ions havingdifferent mass-to-charge ratios. These ions can then be sorted by theirmass-to-charge ratio according to a mass separation parameter, and thesorted ions can subsequently be detected using a dynode configuredaccording to an ion detection parameter. In one embodiment the iondetection parameter can include first and second dynode valuesassociated with first and second time values. In this embodiment thedetecting can comprise acquiring a sample data set that includes a firstabundance of ions acquired during the first time value, and a secondabundance of ions acquired during the second time value. Methods such asthese can be performed utilizing instrumentation described herein.

In particular implementations, the combination of a dynode and amultiplier (detector) can be configured for use in field portableinstruments. It can be advantageous, particularly during fieldapplications, to detect both positive and negative ions and therebyprovide a more complete range of analytical flexibility. In particularembodiments the methods and/or circuitry described can be utilized by aninstrument that occupies the least amount of space practical such as aportable or field portable instrument that has dedicated power sourcesand components for use in applications outside the laboratory. Exemplaryfield portable instruments can be those instruments that weigh less thanabout 60 lbs. In other embodiments, field portable instruments includethose instruments that are the general size and configuration of asuitcase. And in still other embodiments, field portable instruments canbe those instruments that utilize less than 500 Watts of electricalpower during periods of peak power demand.

Referring first to FIG. 1, an analytical instrument 10, in accordancewith one embodiment, includes processing circuitry 20, a storage device21, user interface 23, an inlet 24, an ion source 26, a mass separator28, an ion detector 30, and a power source 32. In one implementationanalytical instrument 10 is configured to perform mass spectrometryanalysis operations. Other embodiments are possible includingalternative components in combination with more or less of thecomponents described herein. Exemplary subject samples include inorganicand organic substances in solid, liquid, and/or vapor form. Specificsamples suitable for analysis include volatile compounds such astoluene, semi-volatile compounds such as methyl salicylate, and/or morehighly complex non-volatile protein-based structures such as bradykinin.The samples can be a mixture containing any number of substances or inother aspects samples can be of a substantially pure substance.

Processing circuitry 20 may be implemented as a processor or otherstructure configured to execute executable instructions including, forexample, software and/or firmware instructions. Other exemplaryembodiments of processing circuitry 20 include hardware logic, PGA,FPGA, ASIC, and/or other structures. These examples of processingcircuitry 20 are for illustration and other configurations are possible.In the exemplary embodiment of FIG. 1, circuitry 20 is coupled tostorage device 21 and user interface 23.

Storage device 21 can be configured to store electronic data and/orprogramming such as executable instructions (e.g. software and/orfirmware), data, and/or other digital information and may includeprocessor-usable media. Processor-usable media includes any article ofmanufacture which can contain, store, and/or maintain programming dataand/or digital information for use by, and/or in connection with, aninstruction execution system including processing circuitry 20, in anexemplary embodiment. For example, exemplary processor-usable media mayinclude physical media such as electronic, magnetic, optical,electromagnetic, infrared and/or semiconductor media. Some more specificexamples of processor-usable medium include, but are not limited to, aportable magnetic computer diskette such as a floppy diskette, zip disk,hard drive, random access memory, read only memory, flash memory, cachememory and/or other configurations capable of storing programming, data,and/or other digital information.

User interface 23 can be any interface that allows user manipulationand/or control of instrument 10 and/or provides status information.Exemplary user interfaces include keyboards, monitors, touch-screens,web-based servers, and/or voice activated media.

Processing circuitry 20, in combination with user interface 23, and/orstorage device 21, can be configured to control inlet 24, ion source 26,mass separator 28, detector 30, and/or power source 32 to implementanalysis operations of instrument 10. Processing circuitry 20, incombination with user interface 23 and/or storage device 21, canprovide, in certain embodiments, inlet, ionization, mass separation,and/or detection parameters, to inlet 24, ion source 26, mass separator28, detector 30, and/or power source 32.

Inlet 24 can be configured to introduce a sample for analysis accordingto inlet parameters. Exemplary inlets 24 include, but are not limitedto, batch inlets, direct probe inlets, chromatographic inlets, permeableand/or capillary membrane inlets. Other configurations are possible.Inlet parameters can include values such as chromatographic values. Inthe context of gas chromatography, for example, these inlet parameterscan include, but are not limited to, column type, length, and/ortemperature ramp. Inlet parameters can also include capillary membraneinlet types and/or temperatures, for example. Additional inletparameters can include a time value associated with other inletparameters. For example, and by way of example only, a time value can beassociated with an inlet parameter such as column temperature in theinstance of gas chromatography, or liquid phase composition in theinstance of liquid chromatography. Inlet 24 can be configured to receiveinlet parameters from circuitry 20 and provide sample to ion source 26.

Ion source 26 is coupled to inlet 24 and configured to receive thesample from inlet 24. Ion source 26 is configured to convert componentsof the sample into ions. Exemplary conversion operations may beimplemented by bombarding the sample with electrons, ions, molecules,and/or photons. Conversion operations can also include applying thermaland/or electrical energy. Ion source 26 may be configured to produceions with positive and/or negative charges and/or differentmass-to-charge ratios. For example, sample may be bombarded with a knownchemical species to generate ions having a negative charge and/or samplemay be bombarded with electrons to generate ions having a positivecharge. Samples may also be bombarded with chemical species to generateboth positively and negatively charged ions. Other conversion operationsare possible. Ion source 26 may be configured according to ionizationparameters that include values such as: the amount and type of energyprovided to the sample to form ions; the compositions or chemicalionization applied to the sample to form ions; and/or a time valueassociated with providing this ionization parameter. In one embodimentthe ionization parameter can be associated with other instrumentparameters. For example, a time value ionization parameter can beassociated with a time value inlet parameter, such as the one describedabove. Ions from ion source 26 can be provided to mass separator 28.

Exemplary mass separators 28 can include mass separators such asmagnetic sectors, electrostatic sectors, quadrupole filter sectors,quadrupole ion traps, electrical ion traps, Kingdon traps, linearquadrupole ion traps, ion cyclotron resonance, quadrupole ion trap/timeof flight mass spectrometers, rectilinear ion traps and/or cylindricalion traps (CIT). For example, CITs typically include three components: atrapping volume; and two endcaps. Typically an AC current or RF voltageis applied to the trapping volume at a predefined rate to eject trappedanalytes which are subsequently detected. RF voltage ramps may includevariables such as voltage and/or frequency. Combinations of thesevariables and predefined amounts are typically referred to as waveforms,and waveforms are just one of the many separation parameters that can beapplied to mass separator 28. Generally, waveforms can be optimized toincrease detection of specific analytes of interest such as the ionsformed utilizing ion source 26 according to ionization parameters.Waveforms can also be optimized to allow for multiple stages of massanalysis, for example analyses such as tandem mass spectrometry.

For example, and by way of example only, ions formed using ion source 26can be sorted by their mass-to-charge ratio according to a massseparation parameter that includes waveforms. This mass separationparameter may also be associated with a time value such as a time valuethat is also associated with acquisition parameters such as inlet,ionization, and/or detection parameters. By way of example, anionization parameter that includes values such as a first time value anda first electron impact energy can be associated with a mass separationparameter that has the same first time value associated with a waveform.As stored in storage device 21, processing circuitry 20 can apply theseparameters to both ion source 26 and mass separator 28 and therebyassociate the application of electron impact energy applied by ionsource 26 with the waveform applied by mass separator 28. Device 21 andprocessing circuitry 20 can also be utilized to associate detectionparameters of detector 30.

Detector 30 can be configured to receive analytes from mass separator28. Exemplary detectors include electron multipliers, Faraday cupcollectors, photographic and scintillation type detectors. Detector 30can also include a dynode (not shown in FIG. 1) to convert ions, formedutilizing ion source 26 and received from mass separator 28, intocharged species. During exemplary operation of detector 30, ions arereceived from mass separator 28 by the dynode resulting in the ejectionof charged species. The charged species may then be detected using asingle detector such as an electron multiplier or a combination ofdetectors such as a scintillation/photomultiplier combination. Detector30 can be powered by power source 32.

Power source 32 can include portable and/or stationary power sources (ACor DC). However, where instrument 10 is a portable or field system,power source 32 can be a portable source such as a battery. Power source32 can include two separate, single-channel, ground-referenced powersupplies; a single, dual-channel, ground referenced power supply; and/ora single, dual-channel floating (i.e. not referenced to groundpotential) power supply.

Referring to FIGS. 2 a and 2 b, an aspect of the disclosure providesmass spectrometry circuitry that, in one embodiment, can be utilized todetect ions having different polarities. Instrument circuitry 40includes power supplies 50 and 52 coupled via switch 56 to a dynode 54configured to receive a negatively charged ion 58, in exemplaryembodiments, from a mass separator and/or ion source. In exemplaryaspects switch 56 can be controlled by processing circuitry 20. Switch56 may be embodied as a relay in one exemplary configuration. Circuitry40 can be configured to eject charged species 60 from dynode 54 to anexemplary detector 62. Detector 62 can be configured to have, in certainembodiments, a predefined voltage applied thereto when detector 62 isconfigured as an electron multiplier.

As depicted in FIG. 2 a, providing a positive power supply 50 to dynode54 results in detector 62 being in a negative ion detection mode. Inexemplary embodiments a first voltage is applied between power supply 50and dynode 54. This first voltage can include a positive voltage or avoltage greater than zero. In this mode, negative ion 58 generated, forexample, by ion source 26 (FIG. 1) and provided through mass separator28 (FIG. 1) can be converted to a charged species 60 which can bedetected by an exemplary detector 62. Detector 62 can be configured toprovide a signal that can be received by process circuitry 20 and, inexemplary embodiments, stored in storage device 21.

Alternatively, as depicted in FIG. 2 b, circuitry 40 can be configuredfor positive ion detection. As illustrated in FIG. 2 b negative powersupply 52 is coupled to dynode 54 via switch 56. In this mode when apositive ion 64 is received by dynode 54 a charged species 66 can bedetected by detector 62. This signal as provided above can be providedto process circuitry 20. In one aspect, a negative voltage can beapplied according to the configuration depicted in FIG. 2 b by couplingdynode 54 to negative power supply via switch 56.

In accordance with the present invention, detection parameters caninclude values associated with time that dictate the providing ofpositive voltage between power supply 50 and dynode 54 and atalternative times dictate the providing of negative voltage betweendynode 54 and power supply 52. In accordance with the present inventionthese parameters can be associated via their time values with massseparation parameters, ionization parameters, and/or inlet parameters asthe user defines.

Referring to FIGS. 3 a and 3 b, process circuitry 42 is depicted asexemplarily configured using a single power supply 68. Power supply 68can be a single, dual-channel ground-referenced power supply with apositive output terminal and a negative output terminal for poweringdynode 54 via switch 56. In the exemplary configuration depicted in FIG.3 a, the positive output terminal of power supply 68 is connected todynode 54 via switch 56. Configured as depicted in FIG. 3 a, detector 62is in negative ion detection mode. In this mode negative ion 58 can beconverted to charged species 60 which can be detected by exemplarydetector 62. In the alternative exemplary configuration of FIG. 3 b, thenegative output terminal of power supply 68 is connected to dynode 54.In this configuration positive ion 64 can be received by dynode 54emitting charged species 66 which can be detected by exemplary detector62.

According to another aspect of the disclosure, circuitry 44 is depictedin FIG. 4 b utilizing a floating (i.e. not referenced to groundpotential) power supply 70 according to the exemplary configuration.Power supply 70 includes an output of each polarity. At least someaspects of this configuration can offer the flexibility of allowing thepositive and negative voltages to be set relative to ground, i.e.floated, to provide different voltage levels as instrument conditionswarrant.

Referring to FIG. 4 a, the positive output terminal of power supply 70can be connected to dynode 54 via switch 56. The illustratedconfiguration of FIG. 4 a can provide a positive voltage to dynode 54resulting in detector 62 being in negative detection mode. In this modea negative ion 58 can be converted to charged species 60 which can bedetected by exemplary detector 62. In an alternative configuration, FIG.4 b illustrates the set up for positive ion detection. As depicted inFIG. 4 b, the negative terminal of power supply 70 provides a negativevoltage to dynode 54. In this exemplary configuration positive ions 64can be received by dynode 54 and charged species 66 can be generatedwhich can be detected by exemplary detector 62.

In exemplary embodiments the voltage between the dynode and the powersource can be referenced to the ions being detected. For example, wherethe ions are generated at what may be considered a high voltage, thedynode may be grounded.

The detection of charged species 60 can be utilized to generateanalytical data that includes an abundance of the charged speciesdetected associated with the voltage applied between power source 32 anddynode 54 of detector 30. In certain aspects this analytical data can beassociated with a time value that is likewise associated with timevalues of detection, mass separation, ionization, and/or inletparameters. Referring again to FIGS. 2-4, switch 56 can be controlled byprocessing circuitry 20 and may be embodied as a relay in one exemplaryconfiguration. In these configurations switch 56 is configured in oneposition to apply a first voltage between the dynode and the powersource and in another position to apply second voltage between thedynode and the power source. As exemplarily depicted in FIGS. 2-4 thevoltage between the power source and the dynode in one position can begreater than zero and in another position can be less than zero. In theone position the dynode is configured to eject charged species uponreceipt of negatively charged ions and in the other position the dynodeis configured to eject charged species upon receipt of positivelycharged ions, in one embodiment.

As described above the detection parameter can include first and seconddynode values associated with first and second time values. In exemplaryembodiments the dynode values can include the voltage applied betweenthe power source and the dynode, and the dynode can be configured toreceive negatively charged ions and eject a charged species and/orconfigured to receive positively charged ions and eject a chargedspecies. As described above, in exemplary embodiments, the dynode valuesdo not equal each other. For example, the first dynode value can begreater than zero and a second dynode value can be less than zero. Asexemplarily described above, ions detected during first time values cancomprise negatively charged ions and ions detected during second timevalues can comprise positively charged ions.

Detection parameters can also provide for turning the dynode and/or thedetector off during a time value and turning the dynode and/or thedetector on during another time value. These time values can becoordinated with the time values associated with other acquisitionparameters. For example, these time values can correspond to time valuesof the mass separation parameters described above. In exemplaryembodiments, when associated with mass separation parameters, turningthe dynode and/or detector off during a time value that is associatedwith a mass separation parameter that provides a large flux of ions canextend the useful life of the dynode and/or detector.

In exemplary implementations, applying these parameter values toinstrument 10, as described above, can provide for the acquisition ofanalytical data that is specific to these acquisition parameters. Forexample, and by way of example only, data of known samples can beacquired in accordance with acquisition parameters and utilized asstandard data. Data of unknown samples can be acquired in accordancewith the same acquisition parameters used to acquire the standard dataand then cross referenced by known algorithms to determine qualitativeand quantitative amounts of the known sample present in the unknownsanalyzed.

For example, a first set of acquisition parameters can be provided toinstrument 10 and a known sample analyzed under these acquisitionparameters. This known sample will provide standard data that can beassociated with the known sample. Exemplary data includes massspectrometry data. An unknown sample can also be provided and thissample can be analyzed using these first acquisition parameters. Thedata acquired by analyzing this unknown sample according to these firstacquisition parameters can then be compared with the standard data and apercent match determined according to known mass spectrometryalgorithms. In exemplary embodiments, databases of known sample dataacquired utilizing acquisition parameters can be stored in storagedevice 21 and each one of the data associated with these known samplescan be compared to unknown data acquired using acquisition parameterscorresponding to those used to acquire the known sample data. Thesetypes of analyses are exemplary of analyses that can be utilized todetermine both quantitative and qualitative data.

Referring to FIGS. 5 a and 5 b exemplary data are shown that is acquiredusing embodiments of methods and circuitry described. For example, FIG.5 a represents the mass spectrum of perfluorodimethylcyclohexane (PDCH)acquired using methods and/or circuitry configured as described in thenegative ion detection mode, see e.g., FIGS. 2 a, 3 a, and/or 4 a. ThePDCH spectrum can be acquired, for example, utilizing a dynode voltage+4000 Volts and a multiplier voltage of +1000 Volts. FIG. 5 b representsthe mass spectrum of methyl salicylate acquired using methods and/orcircuitry configured as described in the positive ion detection mode,see, for example, FIGS. 2 b, 3 b, and/or 4 b. The methyl salicylatespectrum can be acquired, for example, utilizing a dynode voltage of−4000 Volts and a multiplier voltage of +1000 Volts.

1. An ion detection method comprising: providing an electron multiplierdetector, the detector being operatively aligned to receive chargedspecies directly from a dynode, wherein the dynode is coupled to a powersource and operatively aligned to receive both first and second ionsfrom an ion source via a mass separator; applying a first voltagebetween the power source and the dynode; contacting the dynode with thefirst ions to create a first charged species; after applying the firstvoltage, applying a second voltage between the power source and thedynode, wherein the second voltage does not equal the first voltage;contacting the dynode with the second ions to create a second chargedspecies; and detecting both the first and second charged species.
 2. Themethod of claim 1 wherein the detector, dynode, ion source, massseparator, and power source are components of a field portable massspectrometer.
 3. The method of claim 2 wherein the detector is coupledto processing circuitry of the mass spectrometer.
 4. The method of claim1 wherein the power source comprises two separate single-channelground-referenced power supplies and the first voltage is supplied fromone power supply and the second voltage is supplied from the other powersupply.
 5. The method of claim 1 further comprising generatinganalytical data, the analytical data comprising an abundance of thecharged species detected associated with the voltage applied between thepower source and the dynode.
 6. The instrument circuitry of claim 1wherein the power source is portable.
 7. The instrument circuitry ofclaim 1 wherein the power source comprises a single dual-channelground-referenced power supply.
 8. The instrument circuitry of claim 1wherein the power source comprises a single dual-channel floating powersupply.
 9. A mass spectrometry analysis method comprising: ionizing asample to form both first and second ions according to an ionizationparameter, the first and second ions having different polarities;sorting the ions by mass-to-charge ratio according to a mass separationparameter; and detecting the sorted ions using a dynode configuredaccording to an ion detection parameter, the ion detection parametercomprising first and second dynode values associated with first andsecond time values, wherein the detecting comprises acquiring a sampledata set comprising a first abundance of ions acquired during the firsttime value and a second abundance of ions acquired during the secondtime value.
 10. The method of claim 9 wherein the dynode is a componentof a field portable mass spectrometer.
 11. The method of claim 9 whereinthe ionization, mass separation, and detection parameters are associatedwith one another.
 12. The method of claim 9 wherein the ionizing thesample comprises exposing the sample to chemical ionization and theionization parameter includes the chemical ionization species of thechemical ionization.
 13. The method of claim 9 wherein the sorting theions comprises providing the ions to an ion trap and the mass separationparameter includes the waveform of the ion trap.